CLENBUTEROL

Overview

Chemical Names

4-AMINO-alpha-[(tert-BUTYLAMINO)METHYL]-3,5-DICHLOROBENZYL ALCOHOL HYDROCHLORIDE

CAS number

21898-19-1 (hydrochloride); 37148-27-9 (clenbuterol)

Functional Class

Veterinary Drug
ADRENOCEPTOR_AGONIST

Evaluations

Evaluation year: 1998

ADI:
0-0.004 µg/kg bw/d

Comments:

The Committee considered the most relevant study for determining the ADI to be that concerning the bronchospasmolytic effect in patients had chronic obstructive airway disease, as these people were likely to be a very sensitive population for this effect. The study's NOEL (2.5 µg/p, 0.04 µg/kg bw) is approximately 25% of the dose in another study in which the inhalation route was used, but in which cardiac effects were not observed. This NOEL is approximately 50% of the oral dose used in another study where, again, cardiac effects did not occur. Hence, this NOEL for the bronchospasmolytic effect offers an additional safety margin for cardiac effects. The Committee established an ADI of 0-0.004 µg/kg bw/d (0.24 µg/p/d for 60-kg adult), based on the NOEL of 0.04 µg/kg bw/d for pharmacodynamic effects in humans and a safety factor of 10. Based on this ADI, the Committee established the following MRLs (expressed as parent drug, in mg/kg tissue, mg/l milk): Muscle and fat (cattle and horses): 0.0002; Liver and kidney (cattle and horses): 0.0006; Milk (cattle): 0.00005. The maximum estimated daily intake level at the MRLs is 0.235 µg/p/d. The Committee recommended that clenbuterol not be used as a growth-promoter in cattle due to the fact that tissue residues of clenbuterol are likely to be substantially in excess of the MRLs, especially in liver.

MRL Comment:

MRLs (expressed as parent drug, in mg/kg tissue, mg/l milk): Muscle and fat (cattle and horses): 0.0002; Liver and kidney (cattle and horses): 0.0006; Milk (cattle): 0.00005

MRL Code:

MRL

Intake:

Maximum daily intake at the MRLs: 0.235 µg/p/d

Meeting:

Report:

TRS 876-JECFA 47/6

Tox Monograph:

FAS 38-JECFA 47/3

Residues:

FNP 41/9-JECFA 47/21

Toxicological study

Pivotal Study:

Clinical study (Nolte & Laumen, 1972; Nolte, 1980): Two groups of patients with COPD: Group A: n=10, COPD from tuberculosis & Group B: n=5, COPD not related to tuberculosis,n=5 with bronchial asthma given single oral doses of 1, 2.5, 5, 10, 20, 25 or 30 µg/person, and after a placebo dose. Group A: reduced intrathoracic gas volume and increased vital capacity and pneumometer values, all dose levels. Group B: reduced airway resistance, with no significant differences from placebo at 1 and 2.5 µg. The pharmacological NOEL in this study was 2.5 µg, equivalent to 0.042 µg/kg bw.

Animal Specie:

Human

Effect:

bronchospasmolysis

NOEL:

2.5 µg/p, 0.04 µg/kg bw

Point of departure: